Xinxin
Qi
a,
Rui
Li
a and
Xiao-Feng
Wu
*ab
aDepartment of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People's Republic of China. E-mail: xiao-feng.wu@catalysis.de
bLeibniz-Institut für Katalyse e.V. an der Universit Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
First published on 27th June 2016
A general and practical strategy has been developed to prepare aurone derivatives. In the presence of the palladium catalyst, 2-iodophenol and terminal alkynes were reacted by using formic acid as the CO source with acetic anhydride as the additive. A variety of aurones were obtained in moderate to good yields. Notably, this is first report on carbonylative synthesis of aurones with formic acid as the CO source.
Recently, palladium-catalyzed carbonylation reaction has drawn much attention for their widely application in both academy and industry.10 In these reactions, CO is used as the cheapest C1 source to prepare the carbonyl-containing compounds. Carbonylative procedures have also been applied in aurones synthesis, however problems such as the selectivity between aurones and flavones and limited substrates testing were not solved.11 Additionally, gaseous CO which is toxic, odorless, flammable and difficult to handle have to be applied. Under this background, various CO surrogates were developed and applied.12 In this regard, we wish to describe here a selective palladium-catalyzed carbonylation reaction of 2-iodophenol and terminal alkynes using formic acid as the CO precursor to provide aurone derivatives.13,14 The reaction proceeds in a selective manner and give the desired aurones in good yields. Notably, this is first report on carbonylative synthesis of aurones with formic acid as the CO source.
Initially, 2-iodophenol and phenyl acetylene was chosen as the model substrates to screen the reaction conditions (Table 1). Fortunately, the aurone product was obtained in 27% yield using Pd(OAc)2 as catalyst, PPh3 as ligand, Et3N as base in toluene at 80 °C (entry 1). Other bases such pyridine, DBU, tBuONa, and NaHCO3 were also studied, and Et3N still give the best results. We then tested different solvents (entries 6–8), toluene proven to be the optimal solvent here. Furthermore, a variety of mono- and bidentate ligands were investigated (entries 9–14), DPPF, DPPPE, and Xphos resulted in similar yields compared with PPh3, 40% and 49% yields were observed by using P(o-tolyl)3 and BuPAd2 (entries 13–14). The yield decreased in the absence of phosphine ligand (entry 15). To our delight, the highest yield can be obtained when the reaction was performed with preformed Pd(PPh3)4 as the catalyst (entry 16).
Entry | Catalyst | Ligand | Base | Solvent | Yieldb (%) |
---|---|---|---|---|---|
a Reaction conditions: 2-iodophenol (1.0 mmol), phenyl acetylene (2.0 mmol), catalyst (3 mol%), ligand (6 mol%), base (5 equiv.), HCOOH (2.0 mmol), acetic anhydride (2.0 mmol), solvent (2 mL), 14 h. b GC yield, with dodecane as the internal standard. c Ligand (4 mol%). | |||||
1 | Pd(OAc)2 | PPh3 | Et3N | Toluene | 27 |
2 | Pd(OAc)2 | PPh3 | Pyridine | Toluene | 25 |
3 | Pd(OAc)2 | PPh3 | DBU | Toluene | 6 |
4 | Pd(OAc)2 | PPh3 | tBuONa | Toluene | 6 |
5 | Pd(OAc)2 | PPh3 | NaHCO3 | Toluene | 24 |
6 | Pd(OAc)2 | PPh3 | Et3N | THF | 9 |
7 | Pd(OAc)2 | PPh3 | Et3N | DMF | 20 |
8 | Pd(OAc)2 | PPh3 | Et3N | CH3CN | 25 |
9c | Pd(OAc)2 | DPPF | Et3N | Toluene | 24 |
10c | Pd(OAc)2 | DPPPE | Et3N | Toluene | 20 |
11c | Pd(OAc)2 | Xantphos | Et3N | Toluene | 18 |
12 | Pd(OAc)2 | XPhos | Et3N | Toluene | 27 |
13 | Pd(OAc)2 | P(o-tolyl)3 | Et3N | Toluene | 40 |
14 | Pd(OAc)2 | BuPAd2 | Et3N | Toluene | 49 |
15 | Pd(OAc)2 | — | Et3N | Toluene | 17 |
16 | Pd(PPh3)4 | — | Et3N | Toluene | 85 |
17 | PdCl2(PPh3)2 | — | Et3N | Toluene | 54 |
With the best reaction conditions in hand, we went on our study with a series of terminal alkynes (Table 2). First, various aromatic alkynes were examined, substrates with electron-donating groups including methoxy, tert-butyl, and methyl gave the corresponding products in very good yields (entries 2–4) those substrates with methyl group substituted at ortho-position gave higher yield than meta- and para- substitution (entry 4, 5 vs. 6). Electron-withdrawing group such as trifluoromethyl provided the desired products in 73% yields (entry 7). Subsequent examination of halide groups showed that fluoro and chloro substitutions resulted in better yields than bromo group (entry 8, 9 vs. 10). Moreover, heteroaryl groups involved thiophene, and pyridine moieties worked well to afford the desired aurone products in good yields (entries 11–12). Furthermore, alkyl alkynes were also tolerated well to provide the target products in good yields (entries 13–15).
Entry | Alkyne | Product | Yieldb (%) |
---|---|---|---|
a Reaction conditions: 2-iodophenol (1.0 mmol), terminal acetylene (2.0 mmol), Pd(PPh3)4 (3 mol%), Et3N (5 equiv.), HCOOH (2.0 mmol), acetic anhydride (2.0 mmol), toluene (2 mL), 12–18 h. b Isolated yields. | |||
1 |
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82 |
2 |
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82 |
3 |
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68 |
4 |
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75 |
5 |
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72 |
6 |
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81 |
7 |
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73 |
8 |
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80 |
9 |
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75 |
10 |
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58 |
11 |
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55 |
12 |
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68 |
13 |
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54 |
14 |
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62 |
15 |
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51 |
Based on the results of aurone synthesis from 2-iodophenol and terminal alkynes, a plausible reaction mechanism was proposed in Scheme 1. Initially, Pd(0) underwent oxidative addition with 2-iodophenol to form arylpalladium species I, and aroylpalladium iodide complex II was formed by the insertion of CO, which generated from formic acid and acetate anhydride. Then alkynes attack and elimination to afford alkynyl ketone intermediate III. Then, Pd(0) inserted to the O–H bond of phenol to provide complex IV, followed by insertion and reductive elimination to give the final aurones V products. However, the insertion of the alkyne into intermediate II followed by cyclopalladation and reductive elimination cannot be excluded.
Footnote |
† Electronic supplementary information (ESI) available: Experimental detail. See DOI: 10.1039/c6ra13615j |
This journal is © The Royal Society of Chemistry 2016 |